Serodominant SARS-CoV-2 Nucleocapsid Peptides Map to Unstructured Protein Regions

Vandervaart, Jacob P.; Inniss, Nicole L.; Ling-Hu, Ted; Minasov, George; Wiersum, Grant; Rosas-Lemus, Monica; Shuvalova, Ludmilla; Achenbach, Chad J.; Hultquist, Judd F.; Satchell, Karla F.; Bachta, Kelly R.

doi:10.1128/spectrum.00324-23

Serodominant SARS-CoV-2 Nucleocapsid Peptides Map to Unstructured Protein Regions

Journal Article · Tue May 16 00:00:00 EDT 2023 · Microbiology Spectrum

DOI:https://doi.org/10.1128/spectrum.00324-23· OSTI ID:2423605

Vandervaart, Jacob P. ^[1]; ^[1]; Ling-Hu, Ted ^[1]; Minasov, George ^[1]; Wiersum, Grant ^[1]; Rosas-Lemus, Monica ^[1]; Shuvalova, Ludmilla ^[1]; ^[1]; ^[1]; ^[1]; ^[1]

Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine

The SARS-CoV-2 nucleocapsid (N) protein is highly immunogenic, and anti-N antibodies are commonly used as markers for prior infection. While several studies have examined or predicted the antigenic regions of N, these have lacked consensus and structural context. Using COVID-19 patient sera to probe an overlapping peptide array, we identified six public and four private epitope regions across N, some of which are unique to this study. We further report the first deposited X-ray structure of the stable dimerization domain at 2.05 Å as similar to all other reported structures. Structural mapping revealed that most epitopes are derived from surface-exposed loops on the stable domains or from the unstructured linker regions. An antibody response to an epitope in the stable RNA binding domain was found more frequently in sera from patients requiring intensive care. Since emerging amino acid variations in N map to immunogenic peptides, N protein variation could impact detection of seroconversion for variants of concern.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2423605

Journal Information:: Microbiology Spectrum, Journal Name: Microbiology Spectrum Journal Issue: 3 Vol. 11; ISSN 2165-0497

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
SARS-Cov-2
epitope
immune response
nucleocapsid
three-dimensional structure
variants of concern

Serodominant SARS-CoV-2 Nucleocapsid Peptides Map to Unstructured Protein Regions

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